Past Mathematical Biology and Ecology Seminar

12 February 2021
14:00
Abstract

Human life expectancy has been increasing steadily over the last century but this has resulted in an increasing incidence of age-related chronic diseases. Over 60% of people over the age of 65 will suffer from more than one disease at the same time (multimorbidity) and 25-50% of those over 80 years old develop frailty, defined as an accumulation of deficits and loss of reserve. Multimorbidity and frailty have complex medical needs and are strongly associated with disability and hospitalization. However, current treatments are suboptimal with problems of polypharmacy due to the fact that each disease is treated individually. Geroprotectors target fundamental mechanisms of ageing common to multiple age-related diseases and shows promise in delaying the onset of multimorbidity and frailty in animal models. However, their clinical testing in patients has been challenging due to the high level of complexity in the mode of action of geroprotectors and in the way multimorbidity and frailty develop.

 The talk will give an overview of these problems and make the case for the use of AI approaches to solve some of those complex issues with a view of designing appropriate clinical trials with geroprotectors to prevent age-related multimorbidity and frailty and extend healthspan.

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  • Mathematical Biology and Ecology Seminar
5 February 2021
14:00
Professor Alexander Anderson
Abstract

Our current approach to cancer treatment has been largely driven by finding molecular targets, those patients fortunate enough to have a targetable mutation will receive a fixed treatment schedule designed to deliver the maximum tolerated dose (MTD). These therapies generally achieve impressive short-term responses, that unfortunately give way to treatment resistance and tumor relapse. The importance of evolution during both tumor progression, metastasis and treatment response is becoming more widely accepted. However, MTD treatment strategies continue to dominate the precision oncology landscape and ignore the fact that treatments drive the evolution of resistance. Here we present an integrated theoretical, experimental and clinical approach to develop treatment strategies that specifically embrace cancer evolution. We will consider the importance of using treatment response as a critical driver of subsequent treatment decisions, rather than fixed strategies that ignore it. Through the integrated application of drug treatments and drug holidays we will illustrate that, evolutionary therapy can drive either tumor control or extinction. Our results strongly indicate that the future of precision medicine shouldn’t be in the development of new drugs but rather in the smarter evolutionary application of preexisting ones.

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  • Mathematical Biology and Ecology Seminar
29 January 2021
14:00
Abstract

Bacteria use intercellular signalling, or quorum sensing (QS), to share information and respond collectively to aspects of their surroundings. The autoinducers that carry this information are exposed to the external environment. Consequently, they are affected by factors such as removal through fluid flow, a ubiquitous feature of bacterial habitats ranging from the gut and lungs to lakes and oceans.

We develop and apply a general theory that identifies and quantifies the conditions required for QS activation in fluid flow by systematically linking cell- and population-level genetic and physical processes. We predict that cell-level positive feedback promotes a robust collective response, and can act as a low-pass filter at the population level in oscillatory flow, responding only to changes over slow enough timescales. Moreover, we use our model to hypothesize how bacterial populations can discern between increases in cell density and decreases in flow rate.

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  • Mathematical Biology and Ecology Seminar
22 January 2021
14:00
Abstract

A major challenge in the study of biological systems is that of model discovery: turning data into reduced order models that are not just predictive, but provide insight into the nature of the underlying system that generated the data. We introduce a number of data-driven strategies for discovering nonlinear multiscale dynamical systems and their embeddings from data.  Such data-driven methods can be used in the biological sciences where rich data streams are affording new possibilities for the understanding and characterization of complex, networked systems.  In neuroscience, for instance, the integration of these various concepts (reduced-order modeling, equation-free, machine learning, sparsity, networks, multi-scale physics and adaptive control) are critical to formulating successful modeling strategies that perhaps can say something meaningful about experiments.   These methods will be demonstrated on a number of neural systems.  I will also highlight how such methods can be used to quantify cognitive and decision-making deficits arising from neurodegenerative diseases and/or traumatic brain injuries (concussions).

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  • Mathematical Biology and Ecology Seminar
4 December 2020
14:00
Abstract

Genotype-phenotype associations can be results of direct effects, genetic nurturing effects and population stratification confounding (The nature of nurture: Effects of parental genotypes, Science, 2018, Deconstructing the sources of genotype-phenotype associations in humans, Science, 2019). Genotypes from parents and siblings of the proband can be used to statistically disentangle these effects. To maximize power, a comprehensive framework for utilizing various combinations of parents’ and siblings’ genotypes is introduced. Central to the approach is mendelian imputation, a method that utilizes identity by descent (IBD) information to non-linearly impute genotypes into untyped relatives using genotypes of typed individuals. Applying the method to UK Biobank probands with at least one parent or sibling genotyped, for an educational attainment (EA) polygenic score that has a R2 of 5.7% with EA, its predictive power based on direct genetic effect alone is demonstrated to be only about 1.4%. For women, the EA polygenic score has a bigger estimated direct effect on age-at-first-birth than EA itself.

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  • Mathematical Biology and Ecology Seminar
27 November 2020
14:00
Abstract

The puzzle-shaped cells that appear in the epidermis of many plants are a striking example of a complex cell shape. Since shape in an organism is often thought to be closely related to its function, it suggests that these unusual shapes must have some functional benefit to the plant. We 
propose that the creation of these complex shapes is an effective strategy to reduce mechanical stress in the cell wall. Although the 
formation of these shapes requires highly anisotropic and non-uniform growth at the sub-cellular level, it appears to be triggered by 
isotropic growth at the organ level. Analysis of cell shape over multiple species is consistent with the idea that the puzzle is in 
response to a developmental constraint, and that the mechanism is like to be conserved among higher plants.

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  • Mathematical Biology and Ecology Seminar
20 November 2020
14:00
Professor Aleksandr Sahakyan
Abstract

 “In this talk, I shall present the past research track passing through quantum mechanical studies of small molecules to biomolecules, to proteome-wide big data analyses and computational genomics. Next, the ongoing research in our group will be presented that builds upon the expertise on different levels of information processing in life (genome, transcriptome, proteins, small molecules), to develop self-consistent “first principles” models in biology with a wide spectrum of usage. The immediate benefits and the targeted processes will be described covering different layers of the central dogma of biology, multigenic diseases and disease driver/passenger mutation predictions."

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  • Mathematical Biology and Ecology Seminar
13 November 2020
14:00
Professor Heather Harrington
Abstract

Signalling pathways can be modelled as a biochemical reaction network. When the kinetics are to follow mass-action kinetics, the resulting
mathematical model is a polynomial dynamical system. I will overview approaches to analyse these models with steady-state data using
computational algebraic geometry and statistics. Then I will present how to analyse such models with time-course data using differential
algebra and geometry for model identifiability. Finally, I will present how topological data analysis can be help distinguish models
and data.

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  • Mathematical Biology and Ecology Seminar
6 November 2020
14:00
Abstract

While the pathological mechanisms in COVID-19 illness are still poorly understood, it is increasingly clear that high levels of pro-inflammatory mediators play a major role in clinical deterioration in patients with severe disease. Current evidence points to a hyperinflammatory state as the driver of respiratory compromise in severe COVID-19 disease, with a clinical trajectory resembling acute respiratory distress syndrome (ARDS) but how this “runaway train” inflammatory response emergences and is maintained is not known. In this talk, we present the first mathematical model of lung hyperinflammation due to SARS- CoV-2 infection. This model is based on a network of purported mechanistic and physiological pathways linking together five distinct biochemical species involved in the inflammatory response. Simulations of our model give rise to distinct qualitative classes of COVID-19 patients: (i) individuals who naturally clear the virus, (ii) asymptomatic carriers and (iii–v) individuals who develop a case of mild, moderate, or severe illness. These findings, supported by a comprehensive sensitivity analysis, points to potential therapeutic interventions to prevent the emergence of hyperinflammation. Specifically, we suggest that early intervention with a locally-acting anti-inflammatory agent (such as inhaled corticosteroids) may effectively blockade the pathological hyperinflammatory reaction as it emerges.

 

 

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  • Mathematical Biology and Ecology Seminar
30 October 2020
14:00
Abstract

Influenza viruses infect millions of individuals each year and cause a significant amount of morbidity and mortality. Understanding how the virus spreads within the lung, how efficacious host immune control is, and how each influences acute lung injury and disease severity is critical to combat the infection. We used an integrative model-experiment exchange to establish the dynamical connections between viral loads, infected cells, CD8+ T cells, lung injury, and disease severity. Our model predicts that infection resolution is sensitive to CD8+ T cell expansion, that there is a critical T cell magnitude needed for efficient resolution, and that the rate of T cell-mediated clearance is dependent on infected cell density. 
We validated the model through a series of experiments, including CD8 depletion and whole lung histomorphometry. This showed that the infected area of the lung matches the model-predicted infected cell dynamics, and that the resolved area of the lung parallels the relative CD8 dynamics. Additional analysis revealed a nonlinear relation between disease severity, inflammation, and lung injury. These novel links between important host-pathogen kinetics and pathology enhance our ability to forecast disease progression.

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  • Mathematical Biology and Ecology Seminar

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